Abstract
Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.
Highlights
Uncontrollable proliferation is a hallmark of cancer cells
It is not surprising that the rate of cell proliferation while organisms are in hibernation or torpid state is drastically decreased, which is consistent with a profound reduction in the synthesis of DNA, RNA, and proteins[8,9,10,11,12,13,14,15,16]
The main aim of the present study is to investigate the anti-proliferative and anti-metastatic effects of hibernating common carp (Cyprinus carpio) plasma on breast cancer cells in vitro and in vivo
Summary
Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. The SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy. Hibernation or torpor is a state of minimal activity and metabolic depression During this state, different organisms enter a specific hypometabolic and dormant state to survive harsh environmental conditions including reduced food supply and low ambient temperature. The plasma of hibernating animals, which has shown a high ability to induce the cell cycle arrest and anti-proliferative effects on cells can be considered as a potential target for cancer therapy
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